Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist.

abstract：:Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Francis S,Croft D,Schüttelkopf AW,Parry C,Pugliese A,Cameron K,Claydon S,Drysdale M,Gardner C,Gohlke A,Goodwin G,Gray CH,Konczal J,McDonald L,Mezna M,Pannifer A,Paul NR,Machesky L,McKinnon H,Bower J

更新日期：2019-04-15 00:00:00

abstract：:The structure-activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia Y,Chackalamannil S,Clasby M,Doller D,Eagen K,Greenlee WJ,Tsai H,Agans-Fantuzzi J,Ahn HS,Boykow GC,Hsieh Y,Lunn CA,Chintala M

更新日期：2007-08-15 00:00:00

abstract：:Glucose transporters (GLUTs) facilitate glucose uptake and are overexpressed in most cancer cells. Inhibition of glucose transport has been shown to be an effective method to slow the growth of cancer cells both in vitro and in vivo. We have previously reported on the anticancer activity of an ester derived glucose up...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roberts DA,Wang L,Zhang W,Liu Y,Shriwas P,Qian Y,Chen X,Bergmeier SC

更新日期：2020-09-15 00:00:00

abstract：:Polymyxin B (1) monohydrochloride was converted to the tetra-BOC derivatives 1b and 1c by reaction with di-tert-butyl dicarbonate. The structures of these protected intermediates were established utilizing a degradative sequence that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenylamines to the free a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weinstein J,Afonso A,Moss E Jr,Miller GH

更新日期：1998-12-01 00:00:00

abstract：:A new class of benzimidazole-5-sulfonamides has been identified as nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Initial structure-activity relationships are presented resulting in compounds 19 and 28 with submicromolar dual functional activity on human and rat receptors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto K,Tatsuta M,Kataoka M,Yasoshima K,Shogase Y,Shimazaki M,Yura T,Li Y,Yamamoto N,Gupta JB,Urbahns K

更新日期：2005-02-01 00:00:00

abstract：:P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

更新日期：2020-09-01 00:00:00

abstract：:Damage to DNA is caused by ionizing radiation, genotoxic chemicals or collapsed replication forks. When DNA is damaged or cells fail to respond, a mutation that is associated with breast or ovarian cancer may occur. Mammalian cells control and stabilize the genome using a cell cycle checkpoint to prevent damage to DNA...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang YL,Lin CY,Shih KC,Huang JW,Tang CY

更新日期：2013-12-01 00:00:00

abstract：:A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Farmer LJ,Bemis G,Britt SD,Cochran J,Connors M,Harrington EM,Hoock T,Markland W,Nanthakumar S,Taslimi P,Ter Haar E,Wang J,Zhaveri D,Salituro FG

更新日期：2008-12-01 00:00:00

abstract：:A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen TK,Ankersen M,Raun K,Hansen BS

更新日期：2001-07-23 00:00:00

abstract：:Emergence of antibioresistance is currently a major threat of public health worldwide. Hence there is an urge need of finding new antibacterial material. Herein, we report a simple and eco-friendly method to synthesize homo and heterodicationic ionic liquids based on quaternary phosphonium and ammonium salt. In order ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brunel F,Lautard C,Garzino F,Raimundo JM,Bolla JM,Camplo M

更新日期：2020-09-15 00:00:00

abstract：:A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Na...

journal_title：Bioorganic & medicinal chemistry letters

authors： Danho W,Swistok J,Cheung AW,Kurylko G,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-02-24 00:00:00

abstract：:A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been synthesized and evaluated for their in vitro cytotoxicity against selected human cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference drug. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tokala R,Bale S,Janrao IP,Vennela A,Kumar NP,Senwar KR,Godugu C,Shankaraiah N

更新日期：2018-06-01 00:00:00

abstract：:Four novel porphyrins containing nitric oxide (NO) donors were synthesized, and the structures of all the products were characterized by IR, UV-vis, (1)H NMR, and elementary analysis. Interestingly, these new compounds not only were able to release NO, but also showed cancer cell-oriented accumulation. Higher accumula...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu W,Liu C,Gong C,Lin W,Guo C

更新日期：2009-03-15 00:00:00

abstract：:We report a rapid method for profiling of kinases using a strategy that couples the merits of combinatorics (in rapid diversity generation) with the throughput attainable using microarrays (in parallel screening). Alanine-scanning, deletion and positional-scanning peptide libraries of a kinase substrate were synthesiz...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uttamchandani M,Chan EW,Chen GY,Yao SQ

更新日期：2003-09-15 00:00:00

abstract：:This communication describes the synthesis and in vitro biological evaluation of novel generation 5 PAMAM dendrimers conjugated with riboflavin as a targeting ligand. Cell-based experiments demonstrated that a dendrimer conjugated with riboflavin is able to undergo cellular binding and uptake in KB cells, and when the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thomas TP,Choi SK,Li MH,Kotlyar A,Baker JR Jr

更新日期：2010-09-01 00:00:00

abstract：:Nine new monoterpene glycosides (1-9), together with 18 known compounds were obtained from the n-butanol soluble fraction of ethanol extract from Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectroscopic data. The inhibitory effects of these compounds (except com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Zhao F,Chen L,Jiang Z,Liu Y,Li Z,Qiu F,Yao X

更新日期：2012-12-01 00:00:00

abstract：:Bromofluoroacetophenone derivatives which produce fluorine substituted phenyl radicals that cleave DNA upon excitation were investigated as a novel photonuclease. Pyrrolecarboxamide-conjugated bromofluoroacetophenones; 4'-bromo-2'-fluoroacetophenone and 2'-bromo-4'-fluoroacetophenone were synthesized and their DNA cle...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wender PA,Jeon R

更新日期：2003-05-19 00:00:00

abstract：:Several efficient synthetic routes for 2-, 4-, and 6-aryl-1,2,4-triazine-3,5-diones were developed. Derivatives were synthesized and studied as gonadotropin-releasing hormone antagonists in an effort to understand structure-activity relationships of the monocyclic compounds. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pontillo J,Guo Z,Wu D,Struthers RS,Chen C

更新日期：2005-10-01 00:00:00

abstract：:A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi MJ,Roh EJ,Hur W,Lee SH,Sim T,Oh CH,Lee SH,Kim JS,Yoo KH

更新日期：2018-12-15 00:00:00

abstract：:A series of 14-deoxy-11,12-didehydroandrographolide analogues were synthesized from naturally occurring andrographolide and their cytotoxicity evaluated against nine cancer cell lines including cholangiocarcinoma. Analogues 5a and 5b exhibited the most potent cytotoxicity with ED50s of 3.37 and 3.08 μM on KKU-M213 cel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sombut S,Bunthawong R,Sirion U,Kasemsuk T,Piyachaturawat P,Suksen K,Suksamrarn A,Saeeng R

更新日期：2017-12-01 00:00:00

abstract：:Carbonic anhydrase inhibitors AZA, EZA, and 4-acetamidobenzsulfonamide were found to inhibit human AQP4-M23 mediated water transport by 80%, 68%, and 23%, respectively, at 20 microM in an in vitro functional assay. AZA was found to have an IC50 against AQP4 of 0.9 microM. Phloretin was inactive under the same conditio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huber VJ,Tsujita M,Yamazaki M,Sakimura K,Nakada T

更新日期：2007-03-01 00:00:00

abstract：:We previously identified o-carborane bisphenol BE360 (4) as a selective estrogen receptor modulator (SERM), which ameliorated bone loss without inducing estrogenic action in uterus of OVX and ORX mice. Here, we synthesized a fluorinated derivative, B-fluorinated o-carborane bisphenol BE310 (5) by means of S(N)Ar react...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2012-07-15 00:00:00

abstract：:Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shook BC,Rassnick S,Chakravarty D,Wallace N,Ault M,Crooke J,Barbay JK,Wang A,Leonard K,Powell MT,Alford V,Hall D,Rupert KC,Heintzelman GR,Hansen K,Bullington JL,Scannevin RH,Carroll K,Lampron L,Westover L,Russell

更新日期：2010-05-01 00:00:00

abstract：:Amino-1,2,5-trideoxy-2,5-imino-D-mannitol was fluorescently tagged by reaction with dansyl chloride at N-1 or by attachment of a dansyl amide bearing spacer to this centre. Compounds obtained are highly potent inhibitors of beta-glucosidase exhibiting Ki values in the single figure nanomolar range. The 1-N-dansyl subs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hermetter A,Scholze H,Stütz AE,Withers SG,Wrodnigg TM

更新日期：2001-05-21 00:00:00

abstract：:5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu CF,Battah S,Kong X,Reeder BJ,Hider RC,Zhou T

更新日期：2015-02-01 00:00:00

abstract：:Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Z,Davies E,Miller WS,Shan S,Valenzano KJ,Kyle DJ

更新日期：2004-11-01 00:00:00

abstract：:A series of N-acyl-N-hydroxy-beta-Phe were designed, synthesized, and shown to have potent inhibitory activity for carboxypeptidase A (CPA). They are the first examples of CPA inhibitors having a hydroxamate functionality. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DH,Jin Y

更新日期：1999-03-08 00:00:00

abstract：:Novel indole-3-heterocycles were designed and synthesized and found to be potent CB1 receptor agonists. Starting from a microsomally unstable lead 1, a bioisostere approach replacing a piperazine amide was undertaken. This was found to be a good strategy for improving stability both in vitro and in vivo. This led to t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison AJ,Adam JM,Baker JA,Campbell RA,Clark JK,Cottney JE,Deehan M,Easson AM,Fields R,Francis S,Jeremiah F,Keddie N,Kiyoi T,McArthur DR,Meyer K,Ratcliffe PD,Schulz J,Wishart G,Yoshiizumi K

更新日期：2011-01-01 00:00:00

abstract：:Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi A,Nguyen TA,Battina SK,Rana S,Takemoto DJ,Chiang PK,Hua DH

更新日期：2008-06-01 00:00:00

abstract：:In order to investigate the relationship between tyrosine phosphorylation of β-catenin and transcriptional activity of β-catenin in Hela and Bcap-37 cells, genistein (a tyrosine kinase inhibitor) was used to inhibit tyrosine phosphorylation in cells. Our results showed the total β-catenin protein levels were mainly eq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qian HY,Zhang DG,Wang HW,Pei DS,Zheng JN

更新日期：2014-06-01 00:00:00